Dietary Marine ω-3 Fatty Acids and Incident Sight-Threatening Retinopathy in Middle-Aged and Older Individuals With Type 2 Diabetes

Abstract

IMPORTANCE Diabetic retinopathy (DR) is a devastating complication of individuals with type 2 diabetes mellitus. The retina is rich in long-chain ω-3 polyunsaturated fatty acids (LCω3PUFAs), which are substrate for oxylipins with anti-inflammatory and antiangiogenic properties. Experimental models support dietary LCω3PUFA protection against DR, but clinical data are lacking. OBJECTIVE To determine whether LCω3PUFA intake relates to a decreased incidence of sight-threatening DR in individuals with type 2 diabetes older than 55 years. DESIGN, SETTING, AND PARTICIPANTS In late 2015, we conceived a prospective study within the randomized clinical trial Prevención con Dieta Mediterránea (PREDIMED), testing Mediterranean diets supplemented with extra virgin olive oil or nuts vs a control diet for primary cardiovascular prevention. The trial was conducted in primary health care centers in Spain. From 2003 to 2009, 3614 individuals aged 55 to 80 years with a previous diagnosis of type 2 diabetes were recruited. Full data were available for 3482 participants (48% men; mean age 67 years). EXPOSURES Meeting the dietary LCω3PUFA recommendation of at least 500 mg/d for primary cardiovascular prevention, as assessed by a validated food-frequency questionnaire. MAIN OUTCOMES AND MEASURES The main outcome was incident DR requiring laser photocoagulation, vitrectomy, and/or antiangiogenic therapy confirmed by an external adjudication committee. RESULTS Of the 3482 participants, 48% were men and the mean age was 67 years. A total of 2611 participants (75%) met target LCω3PUFA recommendation. During a median follow-up of 6 years, we documented 69 new events. After adjusting for age, sex, intervention group, and lifestyle and clinical variables, participants meeting the LCω3PUFA recommendation at baseline (Ն500 mg/d) compared with those not fulfilling this recommendation (<500 mg/d) showed a 48% relatively reduced risk of incident sight-threatening DR, with a hazard ratio of 0.52 (95% CI, 0.31-0.88; P = .001). This association was slightly stronger for yearly updated LCω3PUFA intake (relative risk, 0.48; 95% CI, 0.28-0.82; P = .007). CONCLUSIONS AND RELEVANCE In middle-aged and older individuals with type 2 diabetes, intake of at least 500 mg/d of dietary LCω3PUFA, easily achievable with 2 weekly servings of oily fish, is associated with a decreased risk of sight-threatening DR. Our results concur with findings from experimental models and the current model of DR pathogenesis. TRIAL REGISTRATION clinicaltrials.gov Identifier: http://www.controlled-trials.com /ISRCTN35739639

Vegetarian Diets in the Prevention and Management of Diabetes and Its Complications

“…The potential impact of compromised vitamin D, iron, and calcium levels on diabetes risk, diabetes management, and the development of diabetes comorbidities is not clear. However, adequate intake of the long-chain omega-3 fatty acids EPA and DHA has been associated with some benefits for patients with diabetes, including reduction of albuminuria, improvement in renal function, and risk reduction of diabetic retinopathy (43–45). These fatty acids also have been associated with a lower risk of CVD incidence and mortality among patients with diabetes (46).…”

The role of dyslipidemia in diabetic retinopathy

“…It is hypothesized that the shift from omega-3 fatty acids to omega-6 fatty acids seen in diabetic dyslipidemia causes increased levels of bioactive lipids, which contributes to the pro-inflammatory environment seen in early stages of DR. A recent clinical trial (PREDIMED) demonstrated that dietary intake of long chain omega 3 fatty acids deceased the risk of DR in type 2 diabetic patients (81). One potential explanation for the beneficial effects of omega-3 fatty acids is the synthesis of resolvins.…”

Role of Inflammation in Diabetic Retinopathy:Therapeutic Targets

“…The leukotrienes, products of 5-lipoxygenase, play an important role in leukocyte recruitment and vascular permeability, and they are increased in the vitreous of diabetic patients 17,41 . Recently, a study showed that increased intake of long-chain -3 polyunsaturated fatty acids can decrease the progression of DR 42 , possibly by modulating the amount and type of eicosanoids made 43 .…”